The Dual Immunoregulatory function of Nlrp12 in T Cell-Mediated Immune Response: Lessons from Experimental Autoimmune Encephalomyelitis

Cells
Marjan GharagozlooDenis Gris

Abstract

Although the etiology of multiple sclerosis (MS) remains enigmatic, the role of T cells is unquestionably central in this pathology. Immune cells respond to pathogens and danger signals via pattern-recognition receptors (PRR). Several reports implicate Nlrp12, an intracellular PRR, in the development of a mouse MS-like disease, called Experimental Autoimmune Encephalomyelitis (EAE). In this study, we used induced and spontaneous models of EAE, as well as in vitro T cell assays, to test the hypothesis that Nlrp12 inhibits Th1 response and prevents T-cell mediated autoimmunity. We found that Nlrp12 plays a protective role in induced EAE by reducing IFNγ/IL-4 ratio in lymph nodes, whereas it potentiates the development of spontaneous EAE (spEAE) in 2D2 T cell receptor (TCR) transgenic mice. Looking into the mechanism of Nlrp12 activity in T cell response, we found that it inhibits T cell proliferation and suppresses Th1 response by reducing IFNγ and IL-2 production. Following TCR activation, Nlrp12 inhibits Akt and NF-κB phosphorylation, while it has no effect on S6 phosphorylation in the mTOR pathway. In conclusion, we propose a model that can explain the dual immunoregulatory function of Nlrp12 in EAE. We also propose a model ex...Continue Reading

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Citations

Oct 24, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lindsay S CahillShannon E Dunn
Jul 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Douglas Silva PradoJosé Carlos Alves-Filho
Nov 30, 2019·Frontiers in Immunology·M Elizabeth DeerhakeMari L Shinohara
Feb 17, 2021·Acta Pharmacologica Sinica·Li ChenJian-Ping Zuo

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Methods Mentioned

BETA
flow cytometry
ELISA
transgenic
nuclear translocation

Software Mentioned

Image Lab
FlowJo
CytExpert
NDPview2
GraphPad Prism

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